The pediatric preclinical testing program: Description of models and early testing results

Peter J. Houghton, Christopher L. Morton, Chandra Tucker, Debbie Payne, Edward Favours, Claire Cole, Richard Gorlick, E. Anders Kolb, Wendong Zhang, Richard Lock, Hernan Carol, Mimi Tajbakhsh, C. Patrick Reynolds, John M. Maris, Joshua Courtright, Stephen T. Keir, Henry S. Friedman, Charles Stopford, Joseph Zeidner, Jianrong WuTiebin Liu, Catherine A. Billups, Javed Khan, Sherry Ansher, Jian Zhang, Malcolm A. Smith

Research output: Contribution to journalArticle

301 Citations (Scopus)

Abstract

Background. The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide. Procedures. Solid tumors were grown subcutaneously in immune-deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45-positive cells were enumerated weekly. Results. Vincristine-induced objective responses in 6 of 24 (25%) and cyclophosphamide-induced objective responses in 18 of 28 (64%) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated. Conclusions. We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad-spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity.

Original languageEnglish (US)
Pages (from-to)928-940
Number of pages13
JournalPediatric Blood and Cancer
Volume49
Issue number7
DOIs
StatePublished - Dec 2007

Fingerprint

Program Development
Pediatrics
Neoplasms
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Vincristine
Cyclophosphamide
Heterografts
Rhabdoid Tumor
Ependymoma
Medulloblastoma
Ewing's Sarcoma
Wilms Tumor
Rhabdomyosarcoma
National Cancer Institute (U.S.)
Osteosarcoma
Glioblastoma
Neuroblastoma
Brain Neoplasms
Sarcoma
Kidney

Keywords

  • Cyclophosphamide
  • Developmental therapeutics
  • Preclinical testing
  • Vincristine

ASJC Scopus subject areas

  • Cancer Research
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Houghton, P. J., Morton, C. L., Tucker, C., Payne, D., Favours, E., Cole, C., ... Smith, M. A. (2007). The pediatric preclinical testing program: Description of models and early testing results. Pediatric Blood and Cancer, 49(7), 928-940. https://doi.org/10.1002/pbc.21078

The pediatric preclinical testing program : Description of models and early testing results. / Houghton, Peter J.; Morton, Christopher L.; Tucker, Chandra; Payne, Debbie; Favours, Edward; Cole, Claire; Gorlick, Richard; Kolb, E. Anders; Zhang, Wendong; Lock, Richard; Carol, Hernan; Tajbakhsh, Mimi; Reynolds, C. Patrick; Maris, John M.; Courtright, Joshua; Keir, Stephen T.; Friedman, Henry S.; Stopford, Charles; Zeidner, Joseph; Wu, Jianrong; Liu, Tiebin; Billups, Catherine A.; Khan, Javed; Ansher, Sherry; Zhang, Jian; Smith, Malcolm A.

In: Pediatric Blood and Cancer, Vol. 49, No. 7, 12.2007, p. 928-940.

Research output: Contribution to journalArticle

Houghton, PJ, Morton, CL, Tucker, C, Payne, D, Favours, E, Cole, C, Gorlick, R, Kolb, EA, Zhang, W, Lock, R, Carol, H, Tajbakhsh, M, Reynolds, CP, Maris, JM, Courtright, J, Keir, ST, Friedman, HS, Stopford, C, Zeidner, J, Wu, J, Liu, T, Billups, CA, Khan, J, Ansher, S, Zhang, J & Smith, MA 2007, 'The pediatric preclinical testing program: Description of models and early testing results', Pediatric Blood and Cancer, vol. 49, no. 7, pp. 928-940. https://doi.org/10.1002/pbc.21078
Houghton, Peter J. ; Morton, Christopher L. ; Tucker, Chandra ; Payne, Debbie ; Favours, Edward ; Cole, Claire ; Gorlick, Richard ; Kolb, E. Anders ; Zhang, Wendong ; Lock, Richard ; Carol, Hernan ; Tajbakhsh, Mimi ; Reynolds, C. Patrick ; Maris, John M. ; Courtright, Joshua ; Keir, Stephen T. ; Friedman, Henry S. ; Stopford, Charles ; Zeidner, Joseph ; Wu, Jianrong ; Liu, Tiebin ; Billups, Catherine A. ; Khan, Javed ; Ansher, Sherry ; Zhang, Jian ; Smith, Malcolm A. / The pediatric preclinical testing program : Description of models and early testing results. In: Pediatric Blood and Cancer. 2007 ; Vol. 49, No. 7. pp. 928-940.
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abstract = "Background. The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide. Procedures. Solid tumors were grown subcutaneously in immune-deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45-positive cells were enumerated weekly. Results. Vincristine-induced objective responses in 6 of 24 (25{\%}) and cyclophosphamide-induced objective responses in 18 of 28 (64{\%}) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated. Conclusions. We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad-spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity.",
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AU - Houghton, Peter J.

AU - Morton, Christopher L.

AU - Tucker, Chandra

AU - Payne, Debbie

AU - Favours, Edward

AU - Cole, Claire

AU - Gorlick, Richard

AU - Kolb, E. Anders

AU - Zhang, Wendong

AU - Lock, Richard

AU - Carol, Hernan

AU - Tajbakhsh, Mimi

AU - Reynolds, C. Patrick

AU - Maris, John M.

AU - Courtright, Joshua

AU - Keir, Stephen T.

AU - Friedman, Henry S.

AU - Stopford, Charles

AU - Zeidner, Joseph

AU - Wu, Jianrong

AU - Liu, Tiebin

AU - Billups, Catherine A.

AU - Khan, Javed

AU - Ansher, Sherry

AU - Zhang, Jian

AU - Smith, Malcolm A.

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N2 - Background. The Pediatric Preclinical Testing Program (PPTP) is an initiative supported by the National Cancer Institute (NCI) to identify novel therapeutic agents that may have significant activity against childhood cancers. The PPTP has established panels of childhood cancer xenografts and cell lines to be used for in vivo and in vitro testing. These include panels for Wilms tumor, sarcomas (rhabdomyosarcoma, Ewing sarcoma, and osteosarcoma), neuroblastoma, brain tumors (glioblastoma, ependymoma, and medulloblastoma), rhabdoid tumors (CNS and renal), and acute lymphoblastic leukemia (ALL). Here, we describe the characteristics of the in vivo tumor panels and report results for the in vivo evaluation of two standard agents, vincristine and cyclophosphamide. Procedures. Solid tumors were grown subcutaneously in immune-deficient mice and tumor dimensions were measured weekly. ALL xenografts were inoculated intravenously and human CD45-positive cells were enumerated weekly. Results. Vincristine-induced objective responses in 6 of 24 (25%) and cyclophosphamide-induced objective responses in 18 of 28 (64%) solid tumor models. Comparable assessments of high levels of activity for these two agents were obtained using a tumor growth delay (TGD) measure. Both agents induced regressions in each of the ALL models evaluated. Conclusions. We have established 51 solid tumor and 10 ALL in vivo models. The models identify vincristine and cyclophosphamide as having broad-spectrum activity. The PPTP tumor panels appear to generally recapitulate the activity of these agents against specific childhood cancers and to have the potential for identifying novel agents having significant clinical activity.

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